Alzheimer's disease (AD) is a growing problem worldwide. Since ABCA7’s identification as a risk gene, it has been extensively researched for its role in the disease. We review its recently characterized structure and what the mechanistic insights teach us about its function. We furthermore provide an overview of identified ABCA7 mutations, their presence in different ancestries and protein domains and how they might cause AD. For ABCA7 PTC variants and a VNTR expansion, haploinsufficiency is proposed as the most likely mode‐of‐action, although splice events could further influence disease risk. Overall, the need to better understand expression of canonical ABCA7 and its isoforms in disease is indicated. Finally, ABCA7's potential functions in lipid metabolism, phagocytosis, amyloid deposition, and the interplay between these three, is described. To conclude, in this review, we provide a comprehensive overview and discussion about the current knowledge on ABCA7 in AD, and what research questions remain.Highlights Alzheimer's risk‐increasing variants in ABCA7 can be found in up to 7% of AD patients. We review the recently characterized protein structure of ABCA7. We present latest insights in genetics, expression patterns, and functions of ABCA7.

中文翻译：

---

阿尔茨海默病风险基因 ABCA7 的 ABC

阿尔茨海默氏病 (AD) 是世界范围内一个日益严重的问题。自从ABCA7被鉴定为风险基因后，人们对其在疾病中的作用进行了广泛的研究。我们回顾了它最近表征的结构，以及机械见解告诉我们它的功能。我们还提供了已确定的概述ABCA7突变、它们在不同祖先和蛋白质结构域中的存在以及它们如何导致 AD。为了ABCA7PTC 变异和 VNTR 扩展、单倍体不足被认为是最可能的作用模式，尽管剪接事件可能进一步影响疾病风险。总的来说，需要更好地理解规范的表达ABCA7并指出了其在疾病中的亚型。最后，描述了 ABCA7 在脂质代谢、吞噬作用、淀粉样蛋白沉积以及这三者之间的相互作用中的潜在功能。最后，在这篇综述中，我们对 AD 中 ABCA7 的当前知识以及仍然存在的研究问题进行了全面的概述和讨论。 阿尔茨海默病风险增加的变异ABCA7高达 7% 的 AD 患者中可发现。 我们回顾了最近表征的 ABCA7 蛋白质结构。 我们提出了关于 ABCA7 的遗传学、表达模式和功能的最新见解。